Herbal supplements and methods of use thereof

ABSTRACT

In one embodiment, the present application provides an herbal supplement and method for treating bloating, constipation and/or weight gain in a human subject comprising orally administering to a subject in need thereof an effective amount of the herbal supplement comprising a red quebracho extract. In other embodiments, the supplement may additionally include a triterpenoid saponin, an anti-spasmodic agent, or both.

This application is a Continuation of U.S. application Ser. No.14/072,502, filed Nov. 5, 2013, which claims priority to U.S.Provisional Patent Application No. 61/728,893, filed Nov. 21, 2012. Theentirety of the aforementioned application is incorporated herein byreference.

FIELD

The present application relates to herbal compositions and methods fortreating diseases associated with bloating, constipation and/or weightgain. More particularly, the present application relates to an herbalsupplement and method comprising oral administration of condensedtannins in human subjects for treating bloating, constipation and/orweight gain.

BACKGROUND

Bowel disorders are often characterized by bloating and constipation andare thought to affect at least 20% of the population. Yet, to date noeffective therapy is available. Such bowel disorders include irritablebowel syndrome (IBS), functional constipation, chronicpseudo-obstruction, and chronic abdominal bloating syndrome. Symptomsinclude abdominal pain, constipation, bloating, acid reflux, flatulence,nausea and vomiting, chronic lethargy and sleep disorders.

IBS is a gastrointestinal disorder characterized by chronic abdominalpain and altered bowel habits with either constipation (IBS-C), diarrhea(IBS-D) or both (IBS-M; mixed type). IBS is the most commonly diagnosedGI condition. It is second only to the common cold as a cause of absencefrom work. It is estimated that around 20% of the general populationsuffers from IBS, resulting in increased health care costs. Annualdirect and indirect costs are reported to be of up to $30 billion.

Functional constipation is the most common gastrointestinal complaintaffecting the 63 million Americans with IBS. IBS is often characterizedby hard stools or straining or having fewer than 3 bowel movements aweek at least 25 percent of the time.

Despite the seriousness of IBS as a health care issue the underlyingcauses remain largely unknown. The traditional focus has been onalterations in the GI motility and on visceral hypersensitivity. Recentreports suggest that small intestinal bacterial overgrowth (SIBO) mayplay a significant role in the development of IBS, as well as obesityand type II diabetes. For example, multiple studies have demonstratedexcessive coliform bacteria in the small intestines of IBS patients.

Methanogenic archaebacteria are an important group of gut colonizingbacteria contributing to SIBO that grow primarily under anaerobicconditions and produce methane (CH₄) as a by-product of fermentation.The degradation of carbohydrates by enteric bacteria, includingmethanogenic bacteria, leads to the production of short chain fattyacids (butyrate, propionate, acetate), as well as carbon dioxide,hydrogen and methane. These products are associated with acidic stools,abdominal distension, flatulence, diarrhea, and constipation.Methanogenic bacteria are unique, in that their metabolism increases inthe presence of products from other bacteria. They use hydrogen andammonia from other bacteria as substrates for the production of methane.Intestinal methane production has been linked to IBS-C, functionalconstipation, obesity and type II diabetes. The methane directlyinfluences the colonic transit time, colonic motility, and rectalsensorimotor function resulting in lowered pain threshold.

There is growing evidence that the microbiota plays a critical role inthe determinant of nutrient uptake, energy regulation and ultimatelyweight and metabolic disorders. Gut microbes can influence both theharvest of energy from components of the diet and how energy is storedand expended. In this regard, methane-producing bacteria have been foundto be present in greater abundance in obese mice and humans comparedwith lean animals and individuals. It has been shown that hydrogentransfer between bacterial and archaeal species may increase energyuptake by the large intestine via methanogens by removing fermentationintermediates, such as H₂ or formate. This allows greater production andavailability of short chain fatty acids for absorption across theintestinal lumen. The methane produced also acts as a local paralyticallowing food substrates to have longer contact with the absorptivevilli in the small bowel.

Treatment options for gastrointestinal disorders and obesity arelimited. For example, although there are treatment options for IBSincluding the use of bulking agents, such as fiber, antispasmodics,antidepressants, and more recently probiotics and antibiotics, suchtreatment options are not sufficiently effective and do not treat theunderlying problem. For example, bulking agents have not been shown todemonstrate an improvement in global IB S symptoms and actually havebeen shown to increase bloating and pain. Anti-spasmodics available inthe US for IBS include dicyclomine, hyoscyamine, and peppermint oil. Arecent meta-analysis found only peppermint oil to be effective inimproving global IBS symptoms. Antidepressants have shown poor andconflicting results, ultimately demonstrating no relief in symptoms.Regarding probiotics, a large meta-analysis demonstrated no superioreffect over placebo. And, of course, obesity is an epidemic problem withfew effective options.

Surveys have demonstrated that less than 14% of patients with IBS aresatisfied with their treatment. Presently, there are few dependablepharmaceutical treatment options for IBS or obesity.

In view of the current shortcomings associated with bowel disordertreatments, including IBS and functional constipation, as well asobesity or undesired weight gain, there is a need for new treatments.The present application addresses this need and provides new methods andformulations for treating such disorders or diseases.

SUMMARY

The present application relates to herbal compositions and methods fortreating diseases associated with bloating, constipation and/or weightgain. In one aspect, the present application provides a method fortreating bloating, constipation or weight gain comprising orallyadministering to a human subject in need thereof an herbal supplementcomprising condensed tannins in an amount effective to reduce bloating,constipation and/or weight gain.

In some embodiments, the method employs an herbal supplement comprisinga red quebracho extract. In other embodiments, the supplementadditionally includes either an herbal composition comprising atriterpenoid saponin, an herbal composition comprising an anti-spasmodicagent, or both.

The compositions and methods may be applied to treating bowel disorderscharacterized by bloating or constipation, as well as obesity and otherconditions characterized by undesirable weight gain. Exemplary boweldisorders for treatment include irritable bowel syndrome (IBS),functional constipation and chronic abdominal bloating syndrome. Thecompositions may be further applied to managing or controlling obesityor type II diabetes.

In one embodiment, the herbal supplement comprises a red quebrachoextract and an herbal supplement comprising either a triterpenoidsaponin, an anti-spasmodic agent, or both, wherein the supplement isformulated to reduce bloating, constipation, and/or weight gain. Inanother embodiment, the herbal supplement comprises a red quebrachoextract and a nutraceutically acceptable carrier, wherein the supplementis in the form of a tablet or capsule.

The red quebracho extract may be derived from any red quebracho tree.Exemplary red quebracho species include Shinopsis lorentzii, Schinopsisbalansae, Schinopsis brasiliensis, Schinopsis haenkeana, Schinopsisheterophylla and Schinopsis marginata. Preferably, the supplementcomprises red quebracho extract having a condensed tannin contentbetween about 50% and about 80%. Condensed tannins are known to bind,precipitate and/or shrink proteins, and to negatively impact theactivity of protozoa and methanogenic bacteria.

In certain embodiments, the triterpenoid saponin is provided in the formof a plant extract, such as an Aesculus or Satindus species plantextract. In plants, triterpenoid saponins are considered defensivecompounds against pathogenic microbes and herbivores. Triterpenoidsaponins are useful in view of their antibacterial properties, includingan ability to counteract bacteria and fungi though cell surfaceinteractions therewith and in their ability to complex withcarbohydrates to improve digestibility. In one embodiment, thetriterpenoid saponin is provided in the form of a horse chestnut(Aesculus hippocastanum) extract, soapnut (Satindus trifoliatus)extract, or seed extract thereof.

In some embodiments, the herbal supplement includes one or moreanti-spasmodic agents in the form of an herbal extract derived from aplant. Anti-spasmodic (or spasmolytic) agents prevent or ease spasms orcramps in muscles, and provide particular benefit in the muscles of thegut and bladder of IBS patients, especially in regard to reducingabdominal pain, calming and soothing the digestive system and relaxingthe gastro-esophageal sphincter. Exemplary anti-spasmodic agent sourcesinclude plants, such as barberry, basil, black cohosh, centella,chamomile, cramp bark, dill, fennel, ginger, hawthorn, hops, juniperberries, lemon balm, licorice, marshmallow, nutmeg, peppermint,rosemary, saffron, sage, skullcap, slippery elm, spearmint, thyme,valerian, wild lettuce and wild yam. In one embodiment, theanti-spasmodic agent is provided in the form of a peppermint oil.

In a particular embodiment, the herbal supplement is in a dosage formthat comprises between about 20 to 500 mg of red quebracho extract;between about 100 to about 2000 mg of Aesculus hippocastanum plantextract; and between about 0.05 to about 1 ml of peppermint oil.

DETAILED DESCRIPTION

The following detailed description is presented to enable any personskilled in the art to make and use the present application. For purposesof explanation, specific nomenclature is set forth to provide a thoroughunderstanding of the present application. However, it will be apparentto one skilled in the art that these specific details are not requiredto practice the present application. Descriptions of specificapplications are provided only as representative examples. The presentapplication is not intended to be limited to the embodiments shown, butis to be accorded the widest possible scope consistent with theprinciples and features disclosed herein.

Unless otherwise defined, scientific and technical terms used inconnection with the present application shall have the meanings that arecommonly understood by those of ordinary skill in the art. Further,unless otherwise required by context, singular terms shall includepluralities and plural terms shall include the singular.

DEFINITIONS

As used herein, the following terms shall have the following meanings:

as used herein, the term “herbal composition” is used with reference toany phytochemical or mixture thereof that is obtained, isolated, and/orderived from one or more extracts of plant material(s) or essentialoil(s) thereof. The term “plant material” refers to any plant materialincluding, but not limited to, leaves, hark, stems, flowers, fruits,seeds, roots, and combinations thereof. The terms “herbal extract,” and“plant extract” are used interchangeably with reference to a plantmaterial directly extracted from a plant. An extract may be in the formof a dry powder, solution or oil.

As used herein, the phrase “treating” or “treatment” of weight gain issynonymous with promotion of weight loss, as well as controlling ormanaging body weight, or more specifically, prevention of weight gainand/or inhibiting the promotion of weight gain.

The term “nutraceutically acceptable,” such as in the recitation of a“nutraceutically acceptable carrier,” refers to a material that is notbiologically or otherwise undesirable, i.e., the material may beincorporated into a pharmaceutical composition administered to a patientwithout causing any undesirable biological effects or interacting in adeleterious manner with any of the other components of the compositionin which it is contained.

An “effective amount” refers to a nontoxic but sufficient amount of acomposition or plant material to provide a desired systemic or localeffect. The effective amount will vary with the nature of thecomposition and constituent parts, the age and physical condition of theend user, the severity of the bowel disorder, the duration of thetreatment, the nature of concurrent therapy, the particularpharmaceutically acceptable carrier utilized, and like factors. As usedherein, all percentages are by weight unless otherwise specified.

As used herein the transitional term “comprising” and “comprises” aresynonymous with “including,” “containing,” or “characterized by,” anyone of which is inclusive or open-ended and does not exclude additional,unrecited elements or method steps, regardless of its use in thepreamble or the body of a claim. The term further encompasses the terms“consisting of” and “consisting essentially of”. In the claims and/orthe specification, “comprising” may mean “one,” but it is alsoconsistent with the meaning of “one or more,” “at least one,” and “oneor more than one.”

The present application relates to herbal compositions and methods fortreating bowel disorders associated with bloating, constipation andweight gain. More particularly, the present application relates to anherbal supplement and method comprising oral administration of condensedtannins in human subjects for treating bloating, constipation and/orweight gain. In one embodiment, a method for treating bloating,constipation and/or weight gain comprises orally administering to ahuman subject in need thereof an herbal supplement comprising condensedtannins in an effective amount, wherein the supplement is formulated toreduce bloating, constipation and/or weight gain.

The compositions and methods apply to any bowel disorder characterizedby bloating, constipation, or both, as well as obesity and otherdiseases characterized by unwanted weight gain. Exemplary boweldisorders for treatment include irritable bowel syndrome (IBS),functional constipation, and chronic abdominal bloating syndrome.

In certain embodiments, the compositions and methods relate to treatingone or more symptoms of an IBS disease subtype, including bloatingand/or constipation. According to the Rome III classification system,there are four recognized subtypes of IBS: a) constipation-predominantIBS (IBS-C), characterized by hard or lumpy stools in ≧25% of bowelmovements and loose (mushy) or watery stools in <25% of bowel movements;b) diarrhea-predominant IBS (IBS-D), characterized by loose (mushy) orwater stools in ≧25% of bowel movements and hard or lumpy stools in <25%of bowel movements; and c) mixed-type IBS (IBS-M; sometimes diarrhea,sometimes constipation), characterized by hard or lumpy stools in ≧25%of bowel movements and loose (mushy) or watery stools in ≧25% of bowelmovements; and d) unsubtyped IBS (IBS-U), characterized by insufficientabnormality of stool consistency to meet the criteria for IBS-C, D, orM. Alternating IBS (IBS-A) accounts for a large proportion of patientswhose bowel habit oscillate from diarrhea to constipation and viceversa, such that up to 75% of patients (or more) transition betweenIBS-D and IBS-C over a 1 year period.

In one embodiment, the herbal supplement comprises a red quebrachoextract and an herbal supplement comprising either a triterpenoidsaponin, an anti-spasmodic agent, or both, wherein the supplement isformulated to reduce one or more bowel disorder symptoms in a humansubject, including bloating, constipation or both. Additional symptomstreated by compositions of the present application may include pain;abdominal fullness, abdominal distension; abnormal stool frequency,i.e., fewer than three bowel movements per week or more than three bowelmovements per day; hard or lumpy stools, sometimes loose (mushy) orwatery stools; straining during a bowel movement; urgency (having torush to have a bowel movement); feeling of incomplete bowel movement; orpassing of mucus during a bowel movement.

In a further aspect, the present application provides a method formanaging or controlling weight gain, obesity or type II diabetescomprising orally administering to a human subject in need thereof anherbal supplement as described herein, in an amount effective to reduceweight gain or reduce one or more symptoms of obesity or type IIdiabetes.

The herbal supplement may be prepared using any suitable plantextract(s), preferably at least one known to possess a high condensedtannin content. Condensed tannins are a complex group of polyphenoliccompounds found in a wide variety of plant species. Condensed tannins orproanthocyanidins, are non-branched polymers of flavonoid units (e.g.,flavan-3-ol, flavan-3,4-diol), and usually have a molecular weight ofabout 1-20 kDa.

Condensed tannins bind, precipitate and/or shrink proteins and have beenshown to reduce methane levels by negatively impacting the activity ofprotozoa and methanogenic bacteria in the gut. In addition, condensedtannins form complexes with carbohydrates and proteins to improveprotein metabolism, improve digestibility and reduce constipation.

The gut microbiota plays an important role in the regulation of energyand weight control and is believed to influence the development andprogression of obesity and type 2 diabetes. Accordingly, the gutmicrobiome further represents a target for condensed tannins, not onlyin the treatment of the above-described bowel disorder, but in thetreatment of obesity and/or type II diabetes as well.

Plant parts containing tannins include bark, wood, fruit, fruitpods,leaves, roots and plant galls. Condensed tannins may be provided in theform of plant extracts derived from selected plants (and theirrepresentative members), including but not limited to birch (Betulasp.), canaigre (Rumex hymenocephalus), chestnut wood (Castanea sp.,incl. sativa and dentata), Eastern hemlock (Tsuga canadensis),eucalyptus (Eucalyptus sp.), European larch (Latrix decidua), mangrove(Rhizophora sp., incl. mangle), oak (Quercus sp., incl. montana), pine(Pinus sp.), pomegranate (Punica granatum), red quebracho (Schniposissp.), rhatany root (Krameria triandra), Scotch pine bark (Pinussylvestris), spruce (Picea sp., incl. abies), sumac (Rhus sp.), wattle(Acacia sp., incl. decurrens and mearnsii), willow (Salix caprea) andwine grape seed (Vitis vinifera).

In a preferred embodiment, the method employs an herbal supplement inwhich a red quebracho extract provides the condensed tannins. The redquebracho extract may be derived from any red quebracho tree, includingbut not limited to Shinopsis lorentzii, Schinopsis balansae, Schinopsisbrasiliensis, Schinopsis haenkeana, Schinopsis heterophylla andSchinopsis marginata. In one embodiment, the red quebracho extract isprepared from the bark of a red quebracho tree.

In the present application, red quebracho extracts may comprise at least25%, at least 40%, at least 50%, at least 60%, at least 70%, at least80% or at least 90% or more condensed tannins (w/w). In one embodiment,the red quebracho extract is substantially free of hydrolyzable tannins.Alternatively, or in addition, the red quebracho extract is in the formof a powder. In one embodiment, the red quebracho extract is in the formof a powder with a condensed tannin content of at least 80%. Whenadministered in a capsule, the red quebracho extract preferablycomprises a powder, substantially free of hydrolysable tannins andhaving a condensed tannin content of at 50%, at least 60%, at least 70%or about 73%.

The red quebracho extract may be present in any amount sufficient fortreating bloating or constipation. In some embodiments, the herbalsupplement is in a dosage form that comprises red quebracho extract inan amount between about 10 to about 1000 mg, between about 25 to about500 mg, or between about 50 to about 200 mg.

In other embodiments, the herbal supplement additionally includes eitheran herbal composition comprising a triterpenoid saponin, an herbalcomposition comprising an anti-spasmodic agent, or both, wherein thesupplement is formulated to reduce one or more symptoms of a boweldisorder in a human subject characterized by bloating or constipation.In another embodiment, the herbal supplement comprises a red quebrachoextract and a nutraceutically acceptable carrier, wherein the supplementis in the form of a tablet or capsule.

Triterpenoid saponins belong to a large group of structurally diversesurface-active glycoside compounds that are found in a wide variety ofplant species. Triterpenoid saponin compounds typically contain sugarsmoieties in a four or five ring configuration of about 30 carbons withseveral oxygens attached. In plants, triterpenoid saponins areconsidered defensive compounds against pathogenic microbes andherbivores. Triterpenoid saponins are useful in the treatment ofbloating, constipation and/or weight gain in view of their antibacterialproperties, including an ability to counteract bacteria and fungi thoughcell surface interactions therewith and in their ability to complex withcarbohydrates to improve digestibility.

In certain embodiments, the triterpenoid saponin is provided in the formof a plant extract, such as an Aesculus or Sapindus species plantextract. In certain particular embodiments, the triterpenoid saponin isprovided in the form of a horse chestnut (Aesculus hippocastanum)extract or a soapnut (Satindus trifoliatus) extract, including seedextracts thereof.

Anti-spasmodic (or spasmolytic) agents prevent or ease spasms or crampsin muscles, and provide particular benefit in the muscles of the gut andbladder of IBS patients, especially with regard to their ability toreduce abdominal pain, calm and sooth the digestive system, relaxgastrointestinal smooth muscles, relax the gastro-esophageal sphincterand to increase time and absorption of therapeutic agents into the smallintestine. A wide variety of plants are known to naturally synthesizeanti-spasmodic agents.

In some embodiments, the anti-spasmodic agent is provided in the form ofan herbal extract derived from selected plants (and their representativemembers), including but not limited to barberry (Berberis vulgaris),basil (Ocimum basilicum), black cohosh (Actaea racemosa), centella(Centella asiatica), chamomile (Matricaria recutita), cramp bark(Viburnum opulus), dill (Anethum graveolens), fennel (Foeniculumvulgare), ginger (Zingiber officinale), hawthorn (Crataegus monogyna),hops (Humulus lupulus), juniper berries (Juniperus communis), lemon balm(Melissa officinalis), licorice (Glycyrrhiza glabra), marshmallow(Althaea officinalis), nutmeg (Myristica fragrans), peppermint (Menthapiperita), rosemary (Rosmarinus offinalis), saffron (Crocus sativus),sage (Salvia officinalis), skullcap, (Scutellaria baicalensis), slipperyelm (Uhnus rubra), spearmint (Mentha spicata), thyme (Thymus vulgaris),valerian (Valeriana officinale), wild lettuce (Lactuca virosa) and wildyam (Dioscorea villosa).

In a particular embodiment, the anti-spasmodic agent is provided in theform of peppermint oil, a well know flavoring agent derived from theleaves and flowering tops of the Mentha piperita L plant, a hybrid mintthat is a cross between watermint and spearmint.

When used alone, the red quebracho extract may be present in the herbalsupplement in an amount between about 1% to about 100% by weight of thetotal supplement. When used in conjunction with other herbalcompositions described herein, the quebracho extract may be present inthe herbal supplement in an amount between about 0.5% to about 75%,between about 2% to about 40%, or between about 5% to about 20% byweight of the total supplement.

When the herbal composition comprising the triterpenoid saponin isprovided in the form of an herbal extract, the extract may be present inthe herbal supplement in an amount between about 10% to about 90%,between about 20% to 80%, or between about 40% and about 65% by weightof the herbal supplement. In some embodiments, the herbal supplement isin a dosage from that comprises a triterpenoid saponin in an amountbetween about 50 to about 2000 mg, between about 150 to about 1000 mg,or between about 300 to 600 mg.

When the herbal composition comprising the anti-spasmodic agent isprovided in the form of an extract, the extract may be provided in anamount between about 2% to about 70%, more preferably between about 5%to 40%, more preferably between about 15% to about 30% by weight of theherbal supplement. In some embodiments, the herbal composition is in adosage form that comprises the anti-spasmodic agent in an amount betweenabout 10 to about 1000 mg, between about 50 to about 500 mg or betweenabout 100 to about 300 mg.

The herbal supplement may comprises one or more extracts separatelyadministered in combination with one another (e.g. in the form ofcapsules or tablets) or they may be administered together in a singleformulation comprising a red quebracho extract, a triterpenoid saponinand an anti-spasmodic agent.

In one embodiment, the herbal supplement is in a dosage form thatcomprises between about 20 to 500 mg of red quebracho extract; betweenabout 100 to about 2000 mg of Aesculus hippocastanum plant extract; andbetween about 0.05 to about 1 ml of peppermint oil. In a particularembodiment, the herbal supplement comprises 100 mg red quebrachoextract, 470 mg Aesculus hippocastanum extract and 180 mg peppermintoil.

Extracts for use in the present application may be produced from anyplant tissues that can be extracted by water, polar, or petroleumsolvents for treating irritable bowel syndrome. An extract may beprepared using extraction procedures well known in the art (e.g., theuse of organic solvents such as lower alcohols, alkyl esters, alkylethers, alkyl ketones, chloroform, petroleum ether, hexane and/orinorganic solvents such as water). Additionally, the extracts may beproduced by cold extraction techniques using a variety of differentextraction solvents including, but not limited to, water, fatty solvents(such as olive oil), and alcoholic solvents (e.g. 70% ethanol). Coldextraction techniques may be applied to softer parts of the plant suchas leaves and flowers, or in cases wherein the desired active componentsof the plant are heat labile. Alternatively, the aforementioned solventsmay be used to produce extracts of the desired plants by a hotextraction technique, wherein said solvents are heated to a hightemperature, the precise value of said temperature being dependent onthe properties of the chosen solvent, and maintained at that temperaturethroughout the extraction process. Hot extraction techniques are morecommonly applied to the harder, tougher parts of the plant, such asbark, woody branches and larger roots. In some cases, sequentialextractions may be performed in more than one solvent, and at differenttemperatures.

Standard procedures for producing plant extracts (including hotextraction, cold extraction and other techniques) are described in manypublications including “Medicinal plants: a field guide to the medicinalplants of the Land of Israel (in Hebrew), author: N. Krispil, Har Gilo,Israel, 1986” and “Making plant medicine, author: R. Cech, pub. byHorizon Herbs, 2000.” which are incorporated herein by reference intheir entirety. Preferably, the supplement comprises one or more plantextract(s) prepared in powdered form.

Compositions and medicaments containing mixtures of extracts fromdifferent plant species, such as those of the present application may beprepared using different ratios of each extract.

In certain embodiments, the supplement may include an herbal extract inthe form of an essential oil. As used herein, the term “essential oil”refers to an oil derived from herbs or other plants through steamdistillation or cold pressing. An essential oil may be mixed with avegetable oil or water and may be orally ingested for use in accordancewith the present disclosures.

In some cases, leaves from a given plant species may be steam distilledto make the essential oil from that plant species. The essential oilmade from a defined tree species may be used interchangeably for thename of the plant species and for the name of the essential oil producedfrom the leaves and other components of the plant species. Likewise, thesame applies to an extract derived from a given plant species.

The herbal supplement can be provided in any nutraceutically acceptableform. Preferably, the herbal supplement is formulated for oraladministration as, for example but not limited to, drug powders,crystals, granules, small particles (which include particles sized onthe order of micrometers, such as microspheres and microcapsules),particles (which include particles sized on the order of millimeters),beads, microbeads, pellets, pills, microtablets, compressed tablets ortablet triturates, molded tablets or tablet triturates, and in capsules,which are either hard or soft and contain the composition as a powder,particle, bead, solution or suspension.

The herbal supplement can also be formulated for oral administration asa solution or suspension in an aqueous liquid, as a liquid incorporatedinto a gel capsule or as any other convenient formulation foradministration, or for rectal administration, as a suppository, enema orother convenient form. In addition, the compositions of the applicationcan also be provided as a controlled release system.

The herbal supplement may further include any nutraceutically acceptableexcipient, carrier or mixture thereof. As used herein, the term“nutraceutically acceptable excipient or carrier” refers to a non-toxic,inert solid, semi-solid, diluent, encapsulating material or formulationauxiliary of any type. Exemplary excipients include, but are not limitedto diluents or fillers, such as dextrates, dicalcium phosphate, calciumsulfate, lactose, cellulose, kaolin, mannitol, sodium chloride, drystarch, sorbitol, sucrose, inositol, powdered sugar, bentonite,microcrystalline cellulose, or hydroxypropylmethylcellulose may be addedto the inhibitor molecule to increase the bulk of the composition. Also,binders, such as but not limited to, starch, gelatin, sucrose, glucose,dextrose, molasses, lactose, acacia gum, sodium alginate, extract ofIrish moss, panwar gum, ghatti gum, mucilage of isapgol husks,carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, Veegumand starch arabogalactan, polyethylene glycol, ethylcellulose, andwaxes, may be added to the supplement to increase its cohesivequalities. Additionally, lubricants, such as but not limited to, talc,magnesium stearate, calcium stearate, stearic acid, hydrogenatedvegetable oils, polyethylene glycol, sodium benzoate, sodium acetate,sodium chloride, leucine, carbowax, sodium lauryl sulfate, and magnesiumlauryl sulfate may be added to the supplement. Also, glidants, such asbut not limited to, colloidal silicon dioxide or talc may be added toimprove the flow characteristics of a powdered supplement. Finally,disintegrants, such as but not limited to, starches, clays, celluloses,algins, gums, crosslinked polymers (e.g., croscarmelose, crospovidone,and sodium starch glycolate), Veegum, methylcellulose, agar, bentonite,cellulose and wood products, natural sponge, cation-exchange resins,alginic acid, guar gum, citrus pulp, carboxymethylcellulose, or sodiumlauryl sulfate with starch may also be added to facilitatedisintegration of the supplement in the intestine.

In certain embodiments, one or more compositions of the supplement maybe formulated to protect the composition from degradation by the acidicconditions of the stomach and from interactions with proteins, such aspepsin, present in the stomach. Such a formulation may include apH-dependent enteric coating to prevent release until after gastricemptying. Thus, in some embodiments, one or more compositions or theentire supplement is enteric coated. However, in other embodiments nocompositions of the supplement are enteric coated.

An enteric coated composition or supplement may be formulated as entericcoated tablets, beads or granules, which may optionally contain alubricant such as, but not limited to, magnesium stearate.

The enteric coating may include one or more pH dependent polymers. ThepH dependent polymers may remain intact at pH values lower than about4.0 and dissolve at pH values higher than 4.0, preferably higher than5.0, most preferably about 6.0. Exemplary pH-dependent polymers include,but are not limited to, methacarylic acid copolymers, methacrylicacid-methyl methacrylate copolymers (e.g., EUDRAGIT® L100 (Type A),EUDRAGIT® S100 (Type B), Rohm GmbH, Germany; methacrylic acid-ethylacrylate copolymers (e.g., EUDRAGIT® L100-55 (Type C) and EUDRAGIT®L30D-55 copolymer dispersion, Rohm GmbH, Germany); copolymers ofmethacrylic acid-methyl methacrylate and methyl methacrylate (EUIDRAGIT®FS); terpolymers of methacrylic acid, methacrylate, and ethyl acrylate;cellulose acetate phthalates (CAP); hydroxypropyl methylcellulosephthalate (HPMCP) (e.g., HP-55, HP-50, HP-55S, Shinetsu Chemical,Japan); polyvinyl acetate phthalates (PVAP) (e.g., COATERIC®, OPADRY®enteric white OY-P-7171); polyvinylbutyrate acetate; cellulose acetatesuccinates (CAS); hydroxypropyl methylcellulose acetate succinate(HPMCAS), e.g., HPMCAS LF Grade, MF Grade, HF Grade, including AQOAT® LFand AQOAT® MF (Shin-Etsu Chemical, Japan); Shinetsu Chemical, Japan);shellac (e.g., MARCOATTM 125 & MARCOATTM 125N); vinyl acetate-maleicanhydride copolymer; styrene-maleic monoester copolymer; carboxymethylethylcellulose (CMEC, Freund Corporation, Japan); cellulose acetatephthalates (CAP) (e.g., AQUATERIC®); cellulose acetate trimellitates(CAT); and mixtures of two or more thereof at weight ratios betweenabout 2:1 to about 5:1, such as, for instance, a mixture of EUDRAGIT® L100-55 and EUDRAGIT® S 100 at a weight ratio of about 3:1 to about 2:1,or a mixture of EUDRAGIT® L 30 D-55 and EUDRAGIT® FS at a weight ratioof about 3:1 to about 5:1.

The pH dependent polymers can be incorporated in an amount from about10% to 90%, preferably from about 20% to 80% and most preferably fromabout 30% to 70% by weight of the dosage unit or supplement. Thepolymer(s) can be incorporated into the formulation either prior to orafter granulation or they can be added into the supplement either as adry material, or they can be dispersed or dissolved in an appropriatesolvent, and dispersed during granulation.

An enteric coated composition or supplement may include enteric coatedbeads in a capsule, enteric coated microspheres in a capsule, entericcoated microspheres provided in a suspension or mixed with food, whichare particularly convenient for pediatric administration, and entericcoated compressed tablets. The capsule can be a hard-shell gelatincapsule or a cellulose capsule. In particular, the composition or herbalsupplement may be formulated as an enteric coated capsule. In certainembodiments, an herbal supplement comprising an anti-spasmodiccomposition, such as peppermint oil is administered in a tablet formthat is backfilled with microcrystalline cellulose. Alternatively, thepeppermint oil may be administered without the use of an entericcoating.

In some embodiments, the composition(s) and/or supplements may bedirectly compressed, with or without any excipients, into a tablet orother herbal supplement having a nutraceutically acceptable hardness andfriability. Preferably, the directly compressible herbal supplement canbe compressed into tablets having a hardness of greater than 4 kp(kiloponds), preferably a hardness of 8 to 14 kp, more preferably ahardness of 10 to 13 kp. A directly compressible composition can becompressed into a tablet that has a friability of not more than 1% lossin weight, preferably less than 0.8% loss in weight, more preferablyless than 0.5% loss in weight.

The present application is further illustrated by the following Examplethat should not be construed as limiting.

EXAMPLE

A single blinded placebo controlled study includes 20 patientspresenting with active bloating and constipation receiving either aplacebo [N=10] or an herbal supplement [N=10] according to the presentapplication. Endpoints include relief of gas and bloating, andevaluation of constipation and weight loss. Safety profiles and weightchanges are monitored throughout the trial.

The above description is for the purpose of teaching the person ofordinary skill in the art how to practice the present invention, and itis not intended to detail all those obvious modifications and variationsof it which will become apparent to the skilled worker upon reading thedescription. It is intended, however, that all such obviousmodifications and variations be included within the scope of the presentinvention, which is defined by the following claims. The claims areintended to cover the claimed components and steps in any sequence whichis effective to meet the objectives there intended, unless the contextspecifically indicates the contrary.

1. A method for treating bloating, constipation and/or weight gain in ahuman subject, comprising: orally administering to a human subject inneed thereof an effective amount of a herbal supplement comprising a redquebracho extract; an herbal composition comprising a triterpenoidsaponin; and an anti-spasmodic agent, wherein the red quebracho extractis present in the herbal supplement in an amount between about 0.5% toabout 75% by weight of the total supplement, wherein the herbalcomposition is present in the herbal supplement in an amount betweenabout 10% to about 90% by weight of the total supplement, wherein theanti-spasmodic agent is present in the herbal supplement in an amountbetween about 2% to about 70% by weight of the total supplement. 2.(canceled)
 3. (canceled)
 4. The method of claim 1, wherein theanti-spasmodic agent is provided in the form of a peppermint oil. 5.(canceled)
 6. The method of claim 1, wherein the triterpenoid saponin isprovided in the form of an Aesculus or Satindus species plant extract.7. (canceled)
 8. The method of claim 1, wherein the herbal supplement isformulated in a dosage form that comprises between about 20 to 500 mg ofred quebracho extract; between about 0.1 to about 2 g of Aesculushippocastanum plant extract; and between about 0.05 to about 1 ml ofpeppermint oil.
 9. The method of claim 1, wherein the herbal supplementfurther comprises a nutraceutically acceptable carrier.
 10. The methodof claim 1, wherein the human subject suffers from irritable bowelsyndrome, functional constipation, chronic abdominal bloating syndromeor obesity. 11-20. (canceled)
 21. The method of claim 1, wherein theanti-spasmodic agent comprises peppermint.
 22. The method of claim 1,wherein the anti-spasmodic agent is peppermint.
 23. The method of claim1, wherein the red quebracho extract is present in the herbal supplementin an amount between about 2% to about 40% by weight of the totalsupplement, wherein the herbal composition is present in the herbalsupplement in an amount between about 20% to about 80% by weight of thetotal supplement, wherein the anti-spasmodic agent is present in theherbal supplement in an amount between about 5% to about 40% by weightof the total supplement.
 24. The method of claim 1, wherein the redquebracho extract is present in the herbal supplement in an amountbetween about 5% to about 20% by weight of the total supplement, whereinthe herbal composition is present in the herbal supplement in an amountbetween about 40% to about 65% by weight of the total supplement,wherein the anti-spasmodic agent is present in the herbal supplement inan amount between about 15% to about 30% by weight of the totalsupplement.
 25. A method for treating bloating, constipation and/orweight gain in a human subject, comprising: orally administering to ahuman subject in need thereof an effective amount of a herbal supplementcomprising: a red quebracho extract; a nutraceutically acceptablecarrier, and one or more herbal compositions comprising a triterpenoidsaponin, and an anti-spasmodic agent, wherein the herbal supplement isin the form of one or more tablets or capsules, and wherein the herbalsupplement is in a dosage form that comprises 10 to 1000 mg redquebracho extract, 50-2000 mg herbal composition comprising atriterpenoid saponin, and 10-1000 mg anti-spasmodic agent.
 26. Themethod of claim 25, wherein the anti-spasmodic agent comprisespeppermint.
 27. The method of claim 25, wherein the anti-spasmodic agentis peppermint.
 28. The method of claim 25, wherein the herbal supplementis in a dosage form that comprises 25 to 500 mg red quebracho extract,150-1000 mg herbal composition comprising a triterpenoid saponin, and50-500 mg anti-spasmodic agent.
 29. The method of claim 25, wherein theherbal supplement is in a dosage form that comprises 25 to 500 mg redquebracho extract, 50-1000 mg herbal composition comprising atriterpenoid saponin, and 10-1000 mg anti-spasmodic agent.
 30. Themethod of claim 25, wherein the herbal supplement is in a dosage formthat comprises 50 to 200 mg red quebracho extract, 300-600 mg herbalcomposition comprising a triterpenoid saponin, and 100-300 mganti-spasmodic agent.